M9140: All participants will receive 2.8 milligram per kilogram (mg/kg) M9140 intravenously (i.v.) every 3 weeks (q3w) on Day 1 of consecutive 21-day cycles.
Study summary
The PROCEADE PanTumor study aims to investigate M9140 in multiple tumor types which express carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and it is therefore designed as a matrix study. This study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (PK) of M9140 as monotherapy or in combination treatments in adult participants with locally advanced/metastatic CEACAM5 expressing tumors. There will be 3 substudies under this Master Protocol that may be conducted in parallel.
* PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Gastric Cancer (Substudy GC);
* PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Non-Small Cell Lung Cancer (Substudy NSCLC);
* PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants With Advanced Pancreatic Cancer (Substudy PDAC).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Participants are capable of signing informed consent as defined in protocol
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) below or equal to 1
* Participants with adequate hematologic, hepatic and renal function as defined in protocol
* Participant must have at least 1 lesion that is measurable using RECIST v1.1.
* Other protocol defined inclusion criteria could apply
Substudy GC:
* Participants in Part A and Part B with documented histopathological diagnosis of advanced or metastatic, HER2 negative, gastric or GEJ (with an epicenter 2 centimeter (cm) proximal or distal to the GEJ) adenocarcinoma, who were intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage that must have included (provided there is no medical contraindication and these agents are locally approved and available) a fluoropyrimidine and a platinum agent and an Immune checkpoint inhibitors (ICI) for participants with a known microsatellite instability-high (MSI-H) status or participants whose tumor express PD-L1 with a CPS greater than or equal (\>=) 1
* Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2
* Participants in Part A with CEACAM5high GC/GEJC (defined as IHC \>= 2+ staining in \>= 50% of tumor cells)
* Participants in Part B with CEACAM5low GC/GEJC (defined as IHC \>= 2+ staining in less than (\<) 50% of tumor cells)
* Other protocol defined inclusion criteria could apply
Substudy NSCLC:
* Participants in Part A and Part B with histologically or cytologically documented advanced (Stage III not eligible for resection or curative radiation) or metastatic NSCLC with or without driver genomic alterations
* Participants must have been intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage
* Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 3
* Participants who received a platinum-containing regimen or a targeted therapy as (neo)-adjuvant therapy for early-stage disease, if relapse or metastases occurred during or within 3 months after regimen completion, are considered to have received a line of treatment in the advanced setting
* Participants in Part A with CEACAM5 high-expressing EGFR tumors (including participants with any driver genomic alterations other than EGFR mutations
* Participants in Part B with CEACAM5 high known EGFR mutated tumors as assessed according to local clinical practice
* Other protocol defined inclusion criteria could apply
Substudy PDAC:
* Participants with histologically or cytologically confirmed advanced or metastatic PDAC, who were intolerant/refractory to or progressed after systemic therapies for the advanced metastatic stage that must have included (provided there is no medical contraindications, and these agents are locally approved and available; FOLFIRINOX regimen or NALIRIFNOX regimen or Nab-paclitaxel/gemcitabine regimen
* Participants must have received and progressed (according to RECIST 1.1) on at least one 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2
* All participants will be screened using an IHC test to define CEACAM5 expression. Only participants with CEACAM5high expressing tumors will be eligible
* Other protocol defined inclusion criteria could apply
Exclusion Criteria:
* Participant has a history of malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years)
* Participants with known brain metastases, except those meeting the following criteria: Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
* Participants with diarrhea (liquid stool) or ileus Grade \> 1
* Participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, intestinal perforation) and/or bowel obstruction
* Cardiac arrhythmia, unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] \>= II) or a coronary revascularization procedure within 180 days of study entry. Calculated QTc average (using the Fridericia correction calculation) of \> 470 milliseconds (ms)
* Cerebrovascular accident/stroke (\< 6 months prior to enrollment)
* Other protocol defined exclusion criteria could apply
Substudy GC - Participants with prior therapy with irinotecan
Substudy NSCLC:
\- Participants with prior therapy with irinotecan
Substudy PDAC: none
Primary outcome measure(s)
Substudies GC/NSCLC/PDAC: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators — Time from first study treatment to (planned) final assessment at approximately 48 months
Trial sites (81)
Facility
City
Region
Status
University of California - Los Angeles - 300208353
Santa Monica
California
Providence Medical Foundation
Santa Rosa
California
Georgetown University - Lombardi Comprehensive Cancer Center - 1134847
Washington D.C.
District of Columbia
D&H Cancer Research Center
Margate
Florida
Prisma Health Cancer Institute, ITOR, CRU
Greenville
South Carolina
Baptist Cancer Center
Memphis
Tennessee
The University of Texas MD Anderson Cancer Center
Houston
Texas
NEXT Virginia
Fairfax
Virginia
Flinders Medical Centre
Bedford Park
Australia
Nepean Cancer Care Centre
Kingswood
Australia
Mater Misericordiae Ltd - PARENT
South Brisbane
Australia
Macquarie University Hospital - PARENT
Sydney
Australia
Ordensklinikum Linz Krankenhaus der Elisabethinen Linz - Pneumology
Linz
Austria
LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie
Salzburg
Austria
Medical University of Vienna - Department of Internal Medicine
Vienna
Austria
Anhui Provincial Cancer Hospital
Hefei
Anhui
Beijing Cancer Hospital
Beijing
Beijing Municipality
Sun Yat-sen University Cancer Center
Guangzhou
Guangzhou
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan
Hebei
Harbin Medical University Cancer Hospital
Harbin
Heilongjiang
Xiangya Hospital, Central South University
Changsha
Hu'nan
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan
Hubei
Sichuan Cancer Hospital
Chengdu
Sichuan
West China Hospital, Sichuan University
Chengdu
Sichuan
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine - Department of Oncology Surgery
Hangzhou
Zhejiang
Institut Bergonié - Service d'Oncologie Médicale
Bordeaux
France
Centre Georges François Leclerc - Unité de Phase I
Dijon
France
Centre Oscar Lambret - cancerologie generale
Lille
France
Hopital Albert Calmette - CHU Lille - CHU Lille - Institut Coeur Poumon
Lille
France
Hôpital Européen Georges Pompidou - Hématologie Oncologie
Paris
France
Hôpital Saint-Antoine - Oncologie Médicale
Paris
France
ICO - Site René Gauducheau - Service d'Oncologie medicale
Saint-Herblain
France
Hôpital Foch - Service d'Oncologie Médicale
Suresnes
France
Institut Claudius Regaud - Service d'oncologie médicale
Toulouse
France
Institut Gustave Roussy - Pathologie Thoracique
Villejuif
France
Krankenhaus Nordwest GmbH - Neurologische Klinik
Frankfurt am Main
Hesse
St. Josef-Hospital im Katholischen Klinikum Bochum - Haematologie, Onkologie und Palliativmedizin
Bochum
North Rhine-Westphalia
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - I. Medizinische Klinik Gastroenterologie u Hepato.
Mainz
Rhineland-Palatinate
Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.